Radiological feature heterogeneity supports etiological diversity among patient groups in Meniere's disease

We aimed to determine the prevalence of radiological temporal bone features that in previous studies showed only a weak or an inconsistent association with the clinical diagnosis of Meniere's disease (MD), in two groups of MD patients (n = 71) with previously established distinct endolymphatic sac pathologies; i.e. the group MD-dg (ES degeneration) and the group MD-hp (ES hypoplasia). Delayed gadolinium-enhanced MRI and high-resolution CT data were used to determine and compare between and within (affected vs. non-affected side) groups geometric temporal bone features (lengths, widths, contours), air cell tract volume, height of the jugular bulb, sigmoid sinus width, and MRI signal intensity alterations of the ES. Temporal bone features with significant intergroup differences were the retrolabyrinthine bone thickness (1.04 ± 0.69 mm, MD-hp; 3.1 ± 1.9 mm, MD-dg; p < 0.0001); posterior contour tortuosity (mean arch-to-chord ratio 1.019 ± 0.013, MD-hp; 1.096 ± 0.038, MD-dg; p < 0.0001); and the pneumatized volume (1.37 [0.86] cm3, MD-hp; 5.25 [3.45] cm3, MD-dg; p = 0.03). Features with differences between the affected and non-affected sides within the MD-dg group were the sigmoid sinus width (6.5 ± 1.7 mm, affected; 7.6 ± 2.1 mm, non-affected; p = 0.04) and the MRI signal intensity of the endolymphatic sac (median signal intensity, affected vs. unaffected side, 0.59 [IQR 0.31-0.89]). Radiological temporal bone features known to be only weakly or inconsistently associated with the clinical diagnosis MD, are highly prevalent in either of two MD patient groups. These results support the existence of diverse-developmental and degenerative-disease etiologies manifesting with distinct radiological temporal bone abnormalities

Absence of endolymphatic sac ion transport proteins in large vestibular aqueduct syndrome - A human temporal bone study

Hypothesis: Epithelial ion transport pathologies of the endolymphatic sac (ES) are associated with large vestibular aqueduct syndrome (LVAS). Background: LVAS is defined by the pathognomonic features of a widened bony vestibular aqueduct (VA) and an enlarged ES. The underlying cause of its associated cochleovestibular symptoms remains elusive. Disturbances in epithelial ion transport in the enlarged ES, affecting inner ear fluid regulation, were proposed as a possible pathophysiology. However, although respective epithelial ion transport pathologies have been demonstrated in the enlarged ES from transgenic LVAS mouse models, these pathologies have not been investigated in human LVAS cases. Methods: Histological and immunohistochemical analysis of the enlarged ES epithelium in postmortem temporal bones from two individuals with a clinical diagnosis of LVAS. Results: The enlarged ES epithelium demonstrated an overall atypical epithelial differentiation and a lack of the immunolocalization of signature ion transport proteins. Notably, in both cases, a rudimentary branch of the ES with a typically differentiated ES epithelium was present. Conclusions: The described cellular and molecular pathologies of the enlarged ES in humans provide evidence of epithelial transport pathology as one potential cause of cochleovestibular symptoms in LVAS. The present findings also emphasize the clinical relevance of already established LVAS mouse models

Temporal bone histopathology of furosemide ototoxicity

Objectives: To describe the human temporal bone pathology in two patients who incurred furosemide induced ototoxicity. Patients 1) A 46‐year‐old woman in acute liver and renal failure treated with high doses of furosemide for anasarca who developed a rapidly progressive severe‐to‐profound asymmetric sensorineural hearing loss. 2) A 65‐year‐old woman with undifferentiated small cell carcinoma of the lung who received intravenous furosemide 1 day prior to death for pulmonary edema. Interventions Removal of temporal bones, histologic processing, and light microscopy of temporal bones. Main Outcome Measures: Temporal bone histopathology and correlation with clinical and audiometric data. Results: All three temporal bones demonstrated edema and cystic changes in the stria vascularis. In the first case the furosemide exposure was associated with hearing loss and the pathological changes were more extensive including cystic changes in the Hensen's cells, collapse of Reissner's membrane and the tectorial membrane and diffuse loss of inner and outer hair cells with only modest reduction in the spiral ganglion cell population. In the second case, without attributable hearing loss, there was only modest reduction in hair cell and spiral ganglion cell counts. Pathological changes were not observed in the ampullae of the semicircular canals or epithelium of the saccular or utricular maculae in either case. Conclusions: The temporal bone pathologic correlate for furosemide‐induced ototoxicity is edema and cystic degeneration of the stria vascularis. The degree of degenerative change appears dose‐dependent. We infer that pathological changes may occur in the absence of a measurable immediate clinical effect. Level of Evidence NA

Histopathology of the Human Inner Ear in Alström\u27s Syndrome.

Alström\u27s syndrome is an autosomal recessive syndromic genetic disorder caused by mutations in the ALMS1 gene. Sensorineural hearing loss occurs in greater than 85% of patients. Histopathology of the inner ear abnormalities in the human has not previously been fully described. Histopathology of the inner ear in Alström\u27s syndrome is presented in 2 genetically confirmed cases. The predominant histopathologic correlates of the sensorineural loss were degeneration of the organ of Corti, both inner and outer hair cells, degeneration of spiral ganglion cells, and atrophy of the stria vascularis and spiral ligament. © 2015 S. Karger AG, Basel. Audiol Neurotol 2015 20:267-272

Reciprocal Innervation of Outer Hair Cells in a Human Infant

Reciprocal synapses are characterized by the presence of both afferent and efferent types of synaptic specializations between two cells. They have been described at the neural poles of outer hair cells (OHCs) in humans with advanced age and two monkey species. Our objective was to study the innervation of the OHCs and determine if reciprocal synapses were present in a young (8-month-old infant) human subject. We studied the synaptic and cytoplasmic morphology of 162 nerve terminals innervating 29 OHCs using serial section transmission electron microscopy. Seventy-six percent of all OHCs were innervated by terminals with reciprocal synapses. This prevalence increased from the first toward the third row (p < 0.001), and 100% of OHCs in the third row demonstrated at least one reciprocal synapse. The prevalence of terminals with reciprocal synapses was higher in the human infant than in older human subjects and was very similar to what has been reported for the chimpanzee. Reciprocal synapses occur in sufficient numbers to be physiologically significant in primates. The nerve terminals were found to segregate into two groups on the basis of their cytoplasmic morphological characteristics: (1) vesicle-rich/neurofilament-poor (VR/NP) and (2) vesicle-poor/neurofilament-rich (VP/NR). All afferent and reciprocal terminals were of the VP/NR variety. The majority of the efferent terminals originated from VR/NP nerve fibers (classical olivocochlear morphology), but 23.5% of the efferent terminals were VP/NR. The hypothesis that peripheral processes of type II spiral ganglion cells form classical afferent, reciprocal, and a number of purely presynaptic terminals on OHCs is discussed. The presence of different types of synaptic specializations on OHCs formed by nerve fibers of the same type (VP/NR) suggests the existence of reciprocal neuronal circuits between OHCs sharing the dendritic arborization of a type II spiral ganglion cell